Discontinuation of antihypertensive drugs appears to have a detrimental effect, with a recent study reporting that the risk of acute myocardial infarction (AMI) substantially increases after more than 90 days of discontinuation.

Prediagnostic statin exposure appears to be associated with a significant reduction in breast cancer-specific mortality, with the survival benefit being more pronounced in women with oestrogen receptor (ER)-positive tumours, according to a study.

Benzodiazepines confer little to no increase in all-cause mortality risk

Stephen Padilla

14 Jul 2017

Benzodiazepine initiation is associated with either no increase or at most a small increase in the risk of all-cause mortality, results of a recent study based on an intention-to-treat approach suggest. If ever there is a detrimental effect on all-cause mortality, it is likely to be much lower than previously stated and to have uncertain clinical relevance.

“Residual confounding likely explains at least part of the small increase in mortality risk observed in selected analyses,” according to researchers.

There was a 4- (1 to 8 percent) to 9-percent (2 to 7 percent) increase in the risk of mortality related to the initiation of benzodiazepine treatment for follow-ups of 12 and 48 months and in subgroups of younger patients and those starting short acting agents.

“We observed small but statistically significant increases (owing to the large size of the cohort) in mortality risk associated with the initiation of benzodiazepines for follow-ups longer than 6 months, in younger patients, in patients initiating short acting drugs, and in the active comparison with selective serotonin reuptake inhibitor antidepressants,” researchers noted.

These findings do not dismiss the possibility of a modest detrimental effect related to benzodiazepines, but this effect is likely to be much lower than previously reported, they added. [BMJ Open 2012;358:e000850;
BMJ 2014;358:g1996]

“Moreover, the direction and extent of the attenuation of the point estimates with high dimensional propensity score adjustment in both the comparisons with benzodiazepine noninitiators and SSRI initiators, and the tight confidence intervals driven by the large size of our study, suggest that residual confounding—rather than a true effect of benzodiazepine drugs—could drive the small increase in mortality risk observed in selected analyses,” researchers said.

In this retrospective cohort study, 1:1 high dimensional propensity score-matched cohort of benzodiazepine initiators and randomly selected noninitiators with a medical visit within 14 days of the start of benzodiazepine treatment (n=1,252,988) between July 2004 and December 2013 were included.

In addressing treatment barriers and confounding, patients filled one or more prescriptions for any medication in the 90 days and 91 to 180 days prior to the index date, and the high dimensional propensity score was measured on the bases of more than 300 covariates. The main outcome was all-cause mortality, determined by linkage with the Social Security Administration Death Master File.

“Benzodiazepines confer their effects through their action on γ-amino-butyric acid (GABA) type A receptors in the central nervous system, which are molecular substrates for the regulation of vigilance, anxiety, muscle tension, epileptogenic activity, and memory functions,” according to researchers. [Nature 1999;358:796-800]

Discontinuation of antihypertensive drugs appears to have a detrimental effect, with a recent study reporting that the risk of acute myocardial infarction (AMI) substantially increases after more than 90 days of discontinuation.

Prediagnostic statin exposure appears to be associated with a significant reduction in breast cancer-specific mortality, with the survival benefit being more pronounced in women with oestrogen receptor (ER)-positive tumours, according to a study.